Theme 1: The immune system Flashcards

1
Q

The main differences between innate and adaptive immunity

A
  1. Innate: first line of defence. Rapid
    -Basic level of protection
    -Fixed
    -constant during exposure
    -Limited specificity (reaction to all bacteria of a species)
    -No memory
    -Neutrophils

2.Adaptive
-Slow to develop
-Highly specific and respond to wider range of pathogens
-Variable
-Improves upon exposure
-Has memory. Long-lasting protection against infection. T cells, B cells, antibodies

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2
Q

Name and explain physical barriers of the body that prevent infection

A

1-Skin: keratin, high cell turn over, cell-cell junctions with small gaps and little intercellular material, low pH so inhibits growth of pathogens and favours immune cells.
2-Mucosal tissues: secrete mucous to coat bacteria and prevent attachment, ciliated epithelium so cilia eject bacteria, large surface area.
3-Saliva: lysozyme digest cell walls. Lactoferrin removes iron required by bacteria. Antibacterials. Fluid flushes out infection.
4-Urine - flush out pathogens
5-Acidic GI tract with digestive enzymes to inhibit cell growth

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3
Q

Give examples of when physical barriers to infection are compromised

A

1-Toxins from smoking can damage cilia in tissue
2- thickened mucous in cystic fibrosis can lead to lung infections (p. aeruginosa infection)
3-Burnt skin: removes epidermis which causes moist conditions and haem for bacteria. vascular damage inhibits chemotaxis
-Cuts allow opportunistic skin pathogens to enter (s. aureus)
-Surgery can cause sepsis: an excessive acute bacterial infection in the whole body
-Blockage of sebaceous glands and hair follicles can become infected

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4
Q

Why skin has low pH

A

-Fatty acids from sebaceous glands
-Lactic acid from sweat glands

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5
Q

Describe the role of commensal bacteria in host defence at mucosal surfaces

A

-In the gut, they stimulate colonic epithelial cells to give a balanced state called physiological inflammation
-Outcompete pathogens for nutrients, attachment sites and living space
-Some species can produce lactic acid (lactobacilli) and fatty acids (propionibacteria) which kill pathogens

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6
Q

What is the complement system and what 3 functions are involved

A

-it is a cascade that enhances antibodies and phagocytic cells to clear infection. Activated C3 convertase.
-Complement components are proteins in the blood and tissue fluid that cause:

1-Chemotaxis: recruitment of neutrophils to site of infection, causing inflammation
2-Opsonisation: coating bacteria to promote antigen uptake by phagocytes.
3-Membrane attack complex: AMPs disrupt the cell membrane and destroy the pathogen

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7
Q

What are antimicrobial peptides (AMPs) Where are alpha and beta defensins produced. Other example of AMPs

A

-defensins that kill pathogens at mucosal surfaces, by disrupting the cell membranes due to their amphipathic properties.

-⍺ - defensins: made by neutrophils and Paneth cells (epithelial cells in small intestine)
-β - defensins: made by epithelial cells

-lysozyme and phospholipase are also AMPs, made by Paneth cells

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8
Q

What 2 enzymes in tears and saliva digest i) bacterial cell walls and ii) cell membranes

A

i) lysozyme
ii) phospholipase

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9
Q

Paneth cells: where they are found, their function and what do they produce

A

-epithelial cells of the small intestine
-maintain integrity of gut function
-make a-defensins, lysozyme, and phospholipase

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10
Q

What are primary and secondary immune tissues and give examples

A

-Primary: produce immune cells in haematopoiesis.
-Bone marrow and thymus

-Secondary: sites where immune responses are initiated. Antigens are presented here.
-Tonsils, spleen, lymph nodes, Peyer’s patch, MALT

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11
Q

Explain the main process of haematopoiesis

A

-Pluripotent stem cell goes through the myeloid, lymphoid and erythroid lineages.
-Myeloid cell = Erythrocytes Platelets. Granulocytes. Monocytes which then make macrophages and dendritic cells
-Lymphoid cell: T cells. B cells (then plasma and memory) Natural killer cells

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12
Q

What is the thymus, its function and its main structure

A

-A primary immune tissue
-A bilobed organ above the heart
-T cells mature here and are activated before being distributed to secondary lymphoid tissue
-Has a fibrous capsule, with a cortex and medulla. Denser cells in cortex.

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13
Q

What is the lymphatic system. What are lymph nodes. And their different structural components.

A

-Lymphatic system – a system of capillaries, vessels and lymph nodes that transports lymph (extra fluid drained from cells and tissue) and returns it to the venous supply via thoracic duct

-Lymph nodes are secondary lymphoid tissues that contain immune cells to filter the lymph of any debris or pathogens picked up by diseased tissues
-Have a fibrous capsule defining the boundary of the node
- lymphoid follicles containing macrophages and lymphocytes where the immune responses take place
-Follicles have germinal centres for activation of T and B cells.
-Lymph enters via afferent and efferent vessels

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14
Q

What are Peyer’s patches. Structure and function

A

-A secondary lymphoid tissue
-M cells transfer pathogens into Peyer’s patch where it will be identified and generate an immune response by the loose cluster of WBCs beneath the epithelial surface of the small intestines
-destroy pathogens that have entered the gut

-Follicle structure, where immune response is generated. Has no fibrous capsule though.

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15
Q

What do tonsils do and their structure. What is characteristic of the tonsils.

A

-Lymphoid tissue that protect the airways (not the mouth)
-Waldeyer’s ring (palatal, lingual, pharyngeal, adenoids) at the entrance of the pharynx, larynx and gut.
-Underneath the epithelium, are the follicles of lymphatic tissues where the immune responses occur. And mucous-type salivary glands are beneath.

  • Mucous type salivary glands are characteristic of tonsils.
    -And microvilli with deep invaginations of epithelium to increase absorbance of nutrients
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16
Q

What are mucosa associated lymphoid tissue (MALT) Why it is so important

A

-system of small concentrations of lymphoid tissue found in various submucosal membrane sites(GI tract, nasopharynx, thyroid, breast, lung, salivary glands, eye, skin)
-Stimulated lymphocytes move between MALT sites rather than in the general circulation
-very important due to massive surface area of mucous membranes and high load of antigens from food/ air.

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17
Q

Structure and function of monocytes

A

-when they enter tissues, they develop into macrophages which phagocytose pathogens
-Curved horse shoe shaped nucleus. Few granules in cytoplasm

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18
Q

Structure and function of macrophages

A

-long living cells
-Large, some granules, round shape [kinda like a flower]

-Recognizes pathogens then releases cytokines to signal recruitment of neutrophils
to initiate inflammation
-Antigen presenting cells, activate T cells.
-Professional Phagocytes
-Scavenger cells – clear debris and dead cells

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19
Q

Structure and function of neutrophils. How are they recruited. Where they are stored

A

-large granulocytes, very granulated cytoplasm, multilobular nucleus, contain lysosomal enzymes and AMP.
-first responders in innate response. Short living. Most abundant WBC

-Stored in blood and bone marrow
-Neutrophil chemotaxis caused by cytokine signaling produced by macrophages, and complement components.
-influx causes swelling
-Professional phagocytes: engulf microbes by phagocytosis at infected sites to kill them
- are phagocytosed by scavenger macrophages

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20
Q

Structure and function of dendritic cells

A

-have dendrites so spidery structure

-Professional antigen presenting cells: present it in secondary lymphoid tissue to activate T cells and initiate an immune response
-Phagocytose
-Don’t clear infection

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21
Q

Structure and function of mast cells

A

-Lots of granules in cytoplasm
-Involved in mucosal immune defences
-Protect against parasites by releasing histamine, but can cause allergies

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22
Q

Stages of phagocytosis and what is the professional phagocytosers and other cells that can phagocytose

A

1-Recognition by receptors (antigen- complement receptors or receptors that identify antibody coated antigens (Fc) )
2-Engulfment – internalized into phagosome.
3-Phagosome acidified – kills most pathogens
4-Fuses with lysosome to make a phagolysosome.
5-degredation. Lysosymes destroy cell wall. Antigens then released

-Professional phagocytes= monocytes, macrophages and neutrophils
-Also dendritic cells and mast cells.

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23
Q

What cells signal the presence of pathogens to the adaptive immune system

A

Macrophages and dendritic cells

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24
Q

What are the professional antigen presenting cells

A

Dendritic cells, macrophages and B cells

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25
Q

What cells provide immunity to parasites

A

Mast cells, eosinophils and basophils

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26
Q

How immune cells can identify an antigen -The different types of receptors

A

-If it is coated in an antibody, Fc receptors detect this
-Complement receptors
-Pattern recognition receptors (PRRs) recognise pathogen associated molecular patterns (PAMPs)

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27
Q

Describe the main differences between the receptors in the innate and adaptive immunity. (specificity, if expressed in every cell type )

A

1-Innate receptors inherited so the same are expressed in every cell of a particular type.
-Adaptive develop their receptors during an immune response so different cells have different receptors
2-Innate triggers an immediate response unlike the adaptive
3-Innate recognise broad class of pathogens unlike adaptive
4-Innate cannot distinguish between different species, (eg. activated by all gram negative).
-Adaptive discriminate between closely related molecular structures
5-Innate has straight forward genetics. Adaptive make millions of proteins due to their high specificity and requires gene rearrangement. Encoded in multiple genes segments

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28
Q

What are pattern recognition receptors (PRR). Where they are found and on what cells. 3 examples of PRR. What do PRRs recognise

A

-The innate response recognises pathogens via PRRs.
-The receptors are membrane bound or in cytoplasm
-Found in macrophages, neutrophils, dendritic cells, epithelial cells.

-Toll-like receptors (TLR) and NOD-like receptors (NLR) and RLH receptors.
-They recognises and bind pathogen associated molecular patterns (PAMPs) (eg. peptidoglycan, LPS)

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29
Q

What are TLRs, what cells they are found on, pathways, and what are the consequences of mutations in TLR signalling

A

-Toll-like receptors are PRRs in the innate response that recognise pathogens
-mainly expressed in antigen presenting cells (macrophages, dendritic cells, B cells) and in some epithelial cells.
-Either in membrane, detecting extracellular pathogens, or in endoscope, detecting phagosome.

-Different classes recognise different pathogen components. eg:
-TLR4 = LPS
-TLR 3 = double stranded viral RNA
-TLR5 = flagellin

-Cause cytokine, chemokine, AMP, and type I interferon pathways to sustain the innate immunity and activate adaptive.

-Mutations in signalling components lead to immunodeficiencies and recurrent bacterial infections.
-But can be used in anti-inflammatory therapy

30
Q

How do macrophages cause an inflammatory response. What overproduction causes

[Note: cytokines made by macrophages, lymphocytes. Some epithelial cells and connective tissue]

A

-Macrophages detect antigens and their products via PRR receptors
-they secrete pro-inflammatory cytokines which signal different cells.
-Vasodilation to increase chemotaxis, causing swelling and redness.

-Over production causes fever. Fever is a good thing as the increased temperature kills pathogen, and WBCs thrive

31
Q

What is pus

A

-associated with acute infection
-Accumulation of dead/dying neutrophils along with debris from bacteria

32
Q

What is an interferon (IFN). Function. Types. Where they are secreted and how.

A

-signalling molecules that activate the anti-viral immune response by increasing MHC class I, dendritic cells, macrophages, NK, lymphocytes.

-Type 1 interferons (IFN-a and IFN-b) are secreted by most cells, upon viral infection.
-Triggered by the binding of viral nucleic acids to TLR3 receptors.

-Type 2 (IFN-Y) are triggered by cytokines and only found in NK and T cells

33
Q

What type of cells are natural killer cells. How they are activated. Function. How it differs to T and B cells

A

-large granular innate lymphoid cells

-Activated by IFN type 1, IL-12 or TNF-a to kill viruses.
-granules in cytoplasm release enzymes to kill viral infected cells
-Secrete IFN-Y to activate macrophages and T cells
=Links the innate and adaptive immune systems

-Lacks an antigen receptor, unlike B and T cells

34
Q

What are the 4 main phases of host defence against infection

A

1-Physical barrier: skin and mucosal tissues
2-Complement: AMPs, enzymes
3- Innate response: macrophages, granulocytes, NK cells
3- Adaptive response: B cells, antibodies, T cells

35
Q

How is the adaptive immune response activated. Mention MHC molecules

A

-Antigen presenting cells move from infected site to secondary lymphoid tissue and present the antigen to MHC molecules. Form a MHC/ antigen complex
- this is presented to T cells. Only T cells with specific receptors to this complex will bind and get activated.

36
Q

What is autoimmunity

A

-If T cells recognise self antigens, and are not tolerant to them, then this causes immunological attack where the body attacks its own cells and tissues

37
Q

What cells are professional antigen presenting cells. What class of MHC molecule do they express

A

-Dendritic cells, B cells and macrophages
-These are the only cells that express MHC class II molecules

38
Q

Difference between MHC class I and II antigen complexes (what cells express them, intracellular/ extracellular, presented to CD4 or 8 T cells, structure)

A

-Present processed antigens to T cell receptors.

  1. MHC class I = expressed by most nucleated cells (so not RBCs)
    -intracellular antigens are presented by this route
    -present the antigen to cytotoxic CD8 T cells.
    -B2 macroglobin subunit
  2. MHC class II = only expressed by professional antigen presenting cells.
    -extracellular antigens presented by this route
    -presented to CD4 helper T cells
    -made of alpha and beta proteins
39
Q

What is the function of CD4 and CD8 T cells

A

-4= provide help by recruiting other immune cells. (Th1, Tfh etc. all with different effector functions
8= kill infected cells.

8 cannot work without 4

40
Q

what are MHC molecules. What chromosome they are expressed on. function. What is the human MHC genes

A

-transmembrane glycoproteins expressed on the surface of cells.
-encoded by lots of genes on chromosome 6, so great diversity.
-They present processed antigens to T cell receptors, to initiate adaptive immunity.
-Human leukocyte antigens (HLA) are the human MHC genes. Each species has their own unique MHC genes

41
Q

Why the adaptive immune response can recognise a huge range of pathogens

A

-Highly variable cell T and B cell receptors, and diverse MHC molceules due to being expressed on many genes.
-MHC molecules are polygenic and polymorphic

42
Q

What is polymorphism and polygenic

A

-Polygenic: receptors are encoded by lots of different genes so have great diversity. Many possible combinations so many different proteins made, so every individual has different MHC molecules
-Polymorphism: multiple variants (alleles) of each gene exist so increases diversity. Different shapes

43
Q

Structure of T cell receptors and are they polymorphic and/ or polygenic

A

-Composed alpha and beta chains
-Have a variable region = binding site for antigen
-Constant region = provides a scaffold

-These receptors are polygenic but not polymorphic
-A T cell has about 30,000 identical TCRs on its surface, all with identical structure and hence identical antigen specificity

-TCR recognises antigens presented by MHC

44
Q

In what 2 selection processes in the thymus allows the selection of T cells with the correct function

A

1-Positive selection: selecting for T cells that have TCRs that only recognise the MHC/ antigen complex. Those that don’t die via apoptosis.
2-Negative selection: deleting T cells that strongly recognise self antigens, in order to avoid autoimmunity. Those that have a low level of recognition for self antigen survive and move to secondary lymphoid tissue

45
Q

What are naive T cells. What 3 signals are required for their activation.

A

-Naive T cells have not encountered an antigen before so have not been activated. They can only go to secondary lymphoid tissues if activated by 3 signals:
1. antigen/ MHC complex recognition by the TCR.
2. Co-stimulation, by interaction between cell surface receptors
3. Cytokine secretion by antigen presenting cell, to allow differentiation of different T cell subtypes

46
Q

How does the cytokines secreted by the antigen presenting cells regulate CD4 T cell function. Function of Th1, Th2, Th17, Tfh, Treg

A

-The combination of cytokines secreted depends on the PAMPs of the antigen that the immune cell has bound to
-The specific cytokines secreted will activate specific transcription factors which drives proliferation of specific CD4 T cell subtypes with different effector function.

-Th1: macrophage recruitment
-Th2: associate with allergies (mast cells etc.)
-Th17: neutrophils and AMP. Reinforce innate
-Tfh: B cells
-Treg: suppress T cells

47
Q

How are naive CD8 cells activated. Why it differs from CD4. What signal they need once activated

A

-CD8 require the 3 signals (recognition of MHC, co-stimulation & cytokines) just like CD4.
- But they also need the help of CD4 T cells to become activated
-This is because they kill so need extra level of regulation.

-Once activated, they only need to recognise antigen/ MHC complex to kill infected cells

48
Q

Name the T cell growth factor. What it does

A

-Interleukin 2
-The cytokine allows survival of T cells and enabling proliferation and differentiation

49
Q

Describe positive and negative feedback for the regulation of CD4 T cell production

A

Both contribute to the continued proliferation of the T cell:
-Positive: newly polarised T cells make cytokines that feedback to increase further differentiation
-Negative feedback: newly polarised T cells make cytokines that suppress differentiation of other types of T cell

50
Q

How adaptive immunity has memory

A

-When pathogen is eliminated, most T cells die but some T cells persist - these are memory T cells that remember the pathogen.
-This means that their response to secondary infection will be much quicker and bigger.
-This allows long-lasting protective immunity as the pathogen does not have time to replicate

51
Q

What are antibodies made of, their basic structure, what is their function once they bind to antigens

A

-Immunoglobins (Ig)
-Antigen-binding site and a constant region
-Heavy chain and light (lambda & kappa) chain

Recognise and bind antigens which:
-activates complement
-coat antigen to allow other immune cells to bind to it
-neutralises the toxins and masks their function
-prevents pathogens gaining entry into cells

52
Q

What are the 4 classes of immunoglobulin. (IgG, M, A, E) Functions and where they are found. What is responsible for the different classes

A

-The constant region on Ig is responsible for the different classes
1. IgG= most abundant. Monomeric shaped. Made in lymph node, spleen, marrow. Small and flexible (due to hinge region), has many effector functions. Crosses the placenta to protect the foetus
2. IgM= Pentameric star shape. First antibody produced in immune response. In blood and lymph. Activates complement and phagocytosis. IgG will take over.
3. IgA= Dimeric. made by sub-mucosal lymphoid tissues so fights of mucosal infection. Found in gut, saliva, sweat, tears
4. IgE= Combats parasitic infections. Binds to Fc on mast cells, and then antigen binds to it, which activates innate: increased blood flow, neutrophil migration, inflammation. And also muscle contraction (coughing) to defend against parasitic infection in lungs and gut which are far too large to be dealt with by normal immune functions. However can lead to hypersensitivity.

53
Q

What makes B cell receptors (immunoglobulins) highly specific and make 2nd response better

A

-Somatic recombination: creates unique Ig specific to antigens -
-Random rearrangement of different genes (V, D, J, C) come together to form a functional gene. So in each B cell, the combination of genes is unique.
-Gene rearrangement occurs throughout lifetime, creating clonally unique proteins and therefore great diversity of antigen binding sites.

54
Q

What happens between antigen binding to B cell, and an immune response being activated

A
  1. The antigen is taken up by a B cell clone with an antigen specific Ig
  2. B cell presents the antigen to T cells. T cell that responds to the specific antigen will activate the B cell clone.
  3. B cell clone will start to activate and proliferate, and antibodies (specific to the antigen) will be produced.
    [Other B cell clones cannot be activated as have not encountered any activating T cells]
55
Q

What 4 properties make B cells so diverse after encountering antigen (class switching etc.)

A
  1. antigen somatic recombination: gene rearrangement to get unique proteins to recognise specific antigens
  2. class switching: (due to constant region of Ig changing) Same specificity to antigen but different functional characteristics.
    3, somatic hypermutation: point mutations to improve affinity to antigen
  3. switching between membrane bound and secreted antibodies (Ig M etc.): switching from B cell receptor, to acting as an antibody.
56
Q

What is the general effects of ageing and diet on immune function

A

-Ageing: associated with reduced functional reserve capacity in tissues and organs. Ageing sees a progressive decline in most immune cell populations and defects in activation, causing higher susceptibility to disease.
-However elderly people with very healthy diets only see decreased immune function at above 90 years old, so diet has a bigger role to play
-Generally malnutrition decreases lymphocytes, cytokines, antibodies and gut barrier function so higher risk of infection.
-Treating deficiencies enhances immunity however high doses can impair immune function, such as zinc

57
Q

Why is fish oil and vitamin B6 good for you. Why is zinc good for you. What if you have too little zinc

A

-Fish oil has omega 3, shown to reduce PGE and inflammation
-B6 important for lymphocyte and IL2 levels.

-Zinc is important for T and NK cell function, and antibody formation.
-However, too much zinc decreases lymphocytes and copper, and interferes with iron metabolism

58
Q

Which 2 cells have a primary role in the uptake of antigen and its presentation to T-cells

A

Macrophages and B cells

59
Q

Structure and function of B cells

A

-Small & round, with regular nucleus and little cytoplasm
-Professional antigen presenting cells, presents antigen to T cells
-Make antibodies

60
Q

What are the key stages/ molecules in the response to viral infection

A

-Type 1 interferon secretion
-NK cell activation
-Type 2 interferon secretion
-T cells kill infected cells
-Memory cell production

61
Q

What cells have receptors that undergo somatic gene rearrangement

A

T and B cell receptors

62
Q

What metal and what vitamin has the most important effect on immunity

A

Zinc and vitamin B6

63
Q

5 classes of immune diseases and examples

A
  1. Chronic infection (periodontitis, TB)
  2. Autoimmune disease (Crohn’s, rheumatoid arthritis, type 1 diabetes)
  3. Hypersensitivity (allergies)
  4. Metabolic disorder (obesity, type 2 diabetes)
  5. Immunodeficiency (HIV, hyperthyroidism)
64
Q

What is Sjogren’s disease

A

-an autoimmune disease that affects exocrine glands. causes dry mouth and dry eyes. Swelling of salivary glands due to inflammatory response

65
Q

how are metalloproteinases made and their role in periodontitis. What can be used to inhibit this protein

A

-Plaque bacteria induce inflammatory response. Macrophages secrete cytokines which stimulate fibroblasts to secrete MMPs to rearrange bone and connective tissues. Excessive cytokines and MMP causes tissue destruction
-Doxycycline can inhibit MMP

66
Q

How a lateral flow test works for identifying the presence of a pathogen.

A

-A sample of mucus is dipped in a tube containing a solution to dilute the sample, and then placed at one end of a porous strip
-As the sample travels along the strip, it encounters a line of antibodies designed to recognise SARS-CoV-2 antigens on the surface of the virus
-If the antibodies detect the antigens then there is a colour change

67
Q

Professional phagocytes. And other cells that phagocytose

A

-Professional phagocytes= monocytes, macrophages and neutrophils
-Also dendritic cells and mast cells.

68
Q

What is the most abundant Ig in lymph and blood

A

IgG

69
Q

How are activated B cells able to switch between synthesising membrane bound Ig, to secreted Ig (IgM, etc.)

A

-Achieved by alternative mRNA splicing. Splices out the peptide sequence responsible for the membrane component of the Ig

70
Q

What factors affect immune functions (lots)

A

Nutrition, obesity, alchohol, smoking, exercise, stress, gut flora, injury, vaccination history, exposure to pathogens, hormonal status, age, gender